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Drug dosage identifier

Morphine sulphate - IV

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Dose and administration

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Infusion

Morphine (mg) in 50ml IV solution = 50 x weight (kg) x dose (micrograms/kg/hour) 
                                                                      IV rate x 1000

  • Dose is 100 micrograms/kg/hr for 2 hours followed by 25 micrograms/kg/hr thereafter.
  • Lower infusions of 10 -20 micrograms/kg/hr may be used but have not been shown to achieve adequate analgesic levels in preterm infants.

Intermittent Dosing

See Morphine bolus quick reference chart below

  1. 50 - 200 micrograms/kg/dose by slow IV injection, IM or SC. Repeat as required (usually 4-hourly).
  2. Usual starting dose 100 micrograms/kg. Titrate dose against clinical response. Intermittent dosing may lead to intermittent effect.
  3. A bolus of a continuous infusion may be given for short-term additional sedation. This should be charted on the stat drug chart as:
      
    Bolus morphine infusion with the strength specified and the volume and dose specified.
    e.g. For a 1kg baby, "Bolus morphine infusion (25 micrograms/kg in 0.5ml) - dose 2ml (100micrograms) IV"

Indications

  • Analgesia
  • Sedation

Contraindications and precautions

  • Known hypersensitivity to opiates
  • Hypovolaemia, hypotension
  • Caution in preterm infants, especially very immature
  • Caution in neonates with hepatic and renal impairment
  • Caution in neonates with cardiac arrhythmias

Clinical pharmacology

Morphine sulphate is a narcotic analgesic which stimulates opioid receptors in the central nervous system (mimics actions of encephalins and β endorphins). Produces respiratory depression by direct effect upon brain stem respiratory centres. No major effect upon cardiovascular system in analgesic doses. Resistance and capacitance vessels are dilated by the opioids. Gastrointestinal secretions and motility are decreased while tone is increased. Stimulates smooth muscle of biliary and urinary tracts.

Well absorbed from gastrointestinal tract but high first pass hepatic metabolism: parenteral route of administration is preferred. Low binding (20%) to human plasma protein. Hepatic metabolism to glucuronide and other metabolites. Excretion via the kidney - significant amounts of unchanged drug in the neonate. The pharmacokinetics of morphine in the neonate are very variable.

Rapid onset of action after parenteral administration. Peak effect 20-60 minutes. Duration of analgesic effect variable (may persist up to 7 hours). Analgesic effects occur with plasma concentrations 100-150 ng/ml. Respiratory depression may occur with plasma concentrations >300 ng/ml. Accumulation can occur but is rarely a clinical problem.

Possible adverse effects

  • Respiratory depression
  • Gastrointestinal disturbances (ileus and delayed gastric emptying, cramps, constipation).
  • Hypotension
  • Urinary retention
  • Physical dependence

Special considerations

  • Morphine is the drug of choice for most situations requiring pain relief.
  • Administer parenterally appropriate length of time compatible with the infant's needs for analgesia and/or sedation.
  • Wean slowly after prolonged use of morphine, greater than 2 weeks.
  • Management of morphine toxicity: stop morphine, support infant, (ventilation, external cardiac massage, volume expansion etc.), naloxone (0.1 - 0.2 mg/kg/dose IV, or IM).
  • Naloxone is never used for babies at risk of neonatal abstinence syndrome.
  • For certain patients, starting at a lower dose (50 micrograms/kg/hr for the 2-hour loading dose, followed by 10 micrograms/kg/hr) may be more appropriate. During active therapeutic hypothermia, this is desirable as metabolism of medications may be altered. In a non-ventilated patient, a lower dose is less likely to compromise respiratory drive; consider intubating if requiring higher doses to control his/her pain.

Morphine Sulphate quick reference chart

  • This quick reference chart is for rapid drawing up and administration of Morphine sulphate to small babies. 
  • First, dilute 0.1ml of morphine sulphate (5mg/ml, 5000 micrograms/ml) with 0.9ml of sterile water for injection. This gives a diluted solution of 500 micrograms/ml 
  • For infants who weigh more than 2500g, use a 5000 microgram/ml (5mg/ml) ampoule.
Weight (g) Dose (ml) at 50 micrograms/kg Dose (ml) at 100 micrograms/kg
500 0.05 0.10
600 0.06 0.12
700 0.07 0.14
800 0.08 0.16
900 0.09 0.18
1000 0.10 0.20
1100 0.11 0.22
1200 0.12 0.24
1300 0.13 0.26
1400 0.14 0.28
1500 0.15 0.30
1600 0.16 0.32
1700 0.17 0.34
1800 0.18 0.36
1900 0.19 0.38
2000 0.20 0.40
2100 0.21 0.42
2200 0.22 0.44
2300 0.23 0.46
2400 0.24 0.48
2500 0.25 0.50

Management of Morphine Sulphate administration

Description

  • Clear colourless solution 5 mg/ml (=5000 micrograms/1ml) in 1 ml ampoules for IM, IV or SC use.
  • DBL preparation contains no preservative.

Prescription

Stat doses

  1. Charted on the stat page of prescription chart in micrograms/dose.
  2. Maintenance doses are charted on the prescription chart in micrograms/dose.
  3. Bolus doses of a continuous infusion should be charted on the stat page as:
      
    Bolus of morphine infusion with the strength, volume to be administered, and dose in micrograms
    e.g. For a 1kg baby, prescribe "Bolus morphine infusion (25 micrograms/kg in 0.5ml) - dose 2ml (100 micrograms) IV"

Continuous infusion

Charted on the fluid chart giving:

  • dose in micrograms/kg/hour
  • rate in ml/hour.

Also charted on drug chart under continuous infusions giving:

  • amount of drug to be added
  • base fluid, type and volume
  • micrograms/kg/ml

Administration

Slow IV Injection

Administered by nursing staff except the first dose in the non-ventilated postoperative baby.

  • Dilution required if infant <2500g.
    • Dilute 0.1ml morphine sulphate (5mg/ml=5000microgram/ml) with 0.9ml sterile water for injection.
    • This gives a diluted solution of 500 micrograms/ml.
  • Administer by slow IV injection over 5 minutes. Filter prior to administration through a Pall 0.2 micron filter.
  • Is compatible with D5W, D10W, NS. May be co-infused with IV solution, IVN and 0.5 units/ml heparin at Y injection port near infusion site.
  • Do not mix with other drugs, blood or blood products.
  • Flush with NS before and after administration of morphine.

Continuous Infusion

  • Dilute prior to administration.
  • Filter prior to administration through a Pall 0.2 micron filter.
  • Is compatible with D5W, D10W, NS. May be coinfused with, IVN and 0.5 units/ml heparin at Y injection port near infusion site.
  • Administer via a syringe pump.
  • Solution should be changed every 48 hours.

Observation and documentation

  • Evaluate baby's need for and response to medication, analgesic effect up to 7 hours.
  • Monitor for adverse effects.
  • The baby is attached to a continuous cardiorespiratory monitor and managed by a nurse with Neonatal IV Drug Certification.
  • Document heart and respiratory rate hourly.
  • Monitor respiratory status carefully.
  • Provide comfort measures for baby.
  • Record baby's dose out of the narcotic register.
  • Record balance discarded out in the narcotic register.
  • Two nurses must witness the discarding of the unused diluted drug, syringes, and ampoule into the sharps container.
  • Two nurses must sign when discarding any unused drug from a continuous infusion.

Storage

  • Unopened ampoule - stored at room temperature in the narcotic cupboard.
  • Discard as above once opened.

Selected references

  1. Bhat R, Gopal C, Gulati A, Aldana 0, Velamati R, Bhargava H. Pharmacokinetics of a single dose of morphine in preterm infants during the first week of life. J Pediatr 1990; 117:477-81.
  2. Bhat R, Abu-Harb M, Gopal C, Gulati A. Morphine metabolism in acutely ill preterm infants. J Pediatr 1992; 120:795-9.
  3. Lynn AM, Slattery JT. Morphine pharmacokinetics in early infancy. Anesthesiologyr 1987: 66:136-9.
  4. Koren 0, Butt W, Chinyanga H, Soldin S, Tan Y, Pape K. Postoperative morphine infusion in newborn infants: Assessment of deposition characteristics and safety. J Pediatr 1985; 107:963-7.
  5. Hartley R, Levene MI. Opioid pharmacology in the Newborn In: Baillieres Clinical Paediatrics Vol 3, No 3, p 467-493, August 1995.

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Document Control

  • Date last published: 08 April 2019
  • Document type: Drug Dosage Guideline
  • Services responsible: ADHB Pharmacy, Neonatology
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years